Brexpiprazole as Adjunctive Therapy With Major Depressive Disorder and an Inadequate Response to Previous Adjunctive Therapy

Inclusion Criteria:

- Clinical diagnosis of MDD

- In current major depressive episode of ≥ 8 weeks in duration and includes an
inadequate response to at least 1 adjunctive treatment.

- Positive history of at least 1 additional failure to an adequate monotherapy
antidepressant treatment.

- HAM-D17 total score≥ 18

- Currently receiving SSRI of SNRI with adjunctive treatment for at least 6 weeks
before screening.

- Willing to discontinue use of all prohibited psychotropic medications

- Historical positive serological results for HIV, hepatitis B/C

- Able to provide written informed consent prior to the initiation of any
protocol-required procedures

- Subjects who could potentially benefit from adjunctive treatment with Brexpiprazole

Exclusion Criteria:

- Sexually active women of childbearing potential

- Male subjects not practicing 2 different methods of birth control

- Females who are breastfeeding and/or who have a positive pregnancy test result

- Subjects who have received ECT for the current major depressive episode.

- Subjects who have had an inadequate response to ECT

- Current need for involuntary commitment or who have been hospitalized within 4 weeks
of screening

- Current Axis I (DSM-IV-TR)

- Current Axis II (DSM-IV-TR)

- Subjects experiencing hallucinations, delusions, or any psychotic symptomatology in
the current major depressive episode.

- Subjects receiving new onset psychotherapy.

- Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 4, Item 5, or on any
of the 5 C-SSRS Suicidal Behavior Items

- Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the
past 180 days

- Hypothyroidism or hyperthyroidism

- Clinically significant neurological, hepatic, renal, metabolic, haematological,
immunological, cardiovascular, pulmonary, or gastrointestinal disorders

- Currently treated with insulin for diabetes

- Uncontrolled hypertension or symptomatic hypotension, or orthostatic hypotension

- Known ischemic heart disease or history of myocardial infarction, congestive heart
failure, angioplasty, stenting, or coronary artery bypass surgery

- Epilepsy or history of seizures

- Positive drug screen

- The following laboratory test and ECG results are exclusionary:

1. Platelets ≤ 75,000/mm3

2. Hemoglobin ≤ 9 g/dL

3. Neutrophils, absolute ≤ 1000/mm3

4. AST > 2 × ULN

5. ALT > 2 × ULN

6. CPK > 3 × ULN, unless discussed with and approved by the medical monitor

7. Creatinine ≥ 2 mg/dL

8. HbA1c ≥ 7.0%

9. Abnormal free T4 (Note: Free T4 is measured only if result for TSH is abnormal.)

10. QTcF ≥ 470 msec for females and ≥ 450 msec for males

- Treatment with an MAOI or EMSAM within 14 days of the Baseline visit.

- Use of benzodiazepines and/or hypnotics within 7 days prior to the first dose of IMP

- Use of oral neuroleptics within 7 days prior or long-acting approved atypical
antipsychotics ≤ 1 full cycle plus ½ cycle prior to the first dose of IMP

- Subjects who would be likely to require prohibited concomitant therapy during the
trial.

- Subjects who previously participated in any prior brexpiprazole trial

- History of neuroleptic malignant syndrome or serotonin syndrome

- History of true allergic response to more than one class of medications

- Prisoners or subjects who are compulsorily detained for treatment of either a
psychiatric or physical illness.

- Subjects who participated in a clinical trial within the last 180 days or who
participated in more than 2 clinical trials within the past year.

- Any subject who, in the opinion of the investigator or medical monitor, should not
participate.